The present invention relates to an improved method for preparing N-fluorosulfonimides. N-fluorosulfonimides and related compounds can be used in the fluorination of nucleophilic organic compounds such as enolethers, aromatics, and organometallic species.
Fluorine substituents are playing an increasingly important role in the search for new pharmaceutical and agrochemical agents because they modify physicochemical properties and the biological activity of target molecules. See for example BIOMEDICINAL ASPECTS OF FLUORINE CHEMISTRY, Elsevier Biomedical Press, 1982.
Electrophilic fluorination agents allow the introduction of fluorine into target molecules under mild conditions. Fluorination agents containing a nitrogen-fluorine bond are known. U.S. Pat. No. 5,003,074 and E. Differding et al., "New Fluorinating Reagents--The First Enantioselective Fluorination Reaction", Tetrahedron Letters 29(47), 6087 (1988) teach the use of N-fluorosultams in the selective fluorination of carbanions. N-Fluorosultams are disadvantageous because they are insufficiently reactive to fluorinate less reactive nucleophiles such as enol ethers and aromatics.
More reactive N-F reagents are known to react with such nucleophiles, but they suffer from other deficiencies. C. Schack et al., "Substitution and Addition Reactions of NF.sub.4 BF.sub.4 with Aromatic Compounds", J. Fluorine Chem. 18, 363 (1981) teach that NF.sub.4 BF.sub.4 is a useful fluorination agent but access to the NF.sub.4 BF.sub.4 is difficult.
T. Umemoto et al., "N-Fluoropyridinium Triflate and its Analogs, The First Stable 1:1 Salts of Pyridine Nucleus and Halogen Atom", Tetrahedron Letters 27(28), 3271 (1986) and T. Umemoto et al., "Power and Structure-Variable Fluorinating Agents--The N-Fluoropyridinium Salt System", J. Am. Chem. Soc. 112, 8563 (1990) teach that N-fluoropyridinium salts are useful fluorinating agents but unfortunately they undergo side-reactions with carbanionic nucleophiles.
R. Banks et al., "N-Halogeno Compounds--Part II--Perfluoro-[N-fluoro-N-(4-pyridyl)-methanesulphonamide]--A Powerful New Electrophilic Fluorinating Agent", J. Fluorine Chem. 46, 297 (1990) teaches that perfluoro-[N-fluoro-N-(4-pyridyl)methanesulphonamide] is a useful fluorinating agent. Unfortunately, the preparation of perfluoro-[N-fluoro-N-(4-pyridyl)methanesulphonamide] involves at least six steps and perfluoro-[N-(4-pyridyl)methanesulphonamide] cannot be used with aromatic solvents such as benzene or toluene because it reacts with these solvents.
N-Fluorosulfonamides are known to be useful as fluorinating agents. For example, U.S. Pat. No. 4,479,901; M. Sequin et al., "Action de CF.sub.3 of Sur Des Aziridines N-Substituees", J. Fluorine Chem. 15, 201 (1980); W. Barnette, "N-Fluoro-N-alkylsulfonamides: Useful Reagents for the Fluorination of Carbanions", J. Am. Chem. Soc. 106, 452 (1984); and U.S. Pat. No. 4,900,867 teach that N-fluoro-N-alkylsulfonamides such as N-fluoro-N-neopentyl-p-toluenesulfonamide are useful in the fluorination at a carbon atom of a carbanion. S. Lee et al., "Stereospecific Synthesis of Alkenyl Fluorides (with Retention) via Organometallic Intermediates", J. Am. Chem. Soc. 108, 2445 (1986) teach that N-fluoro-N-alkylsulfonamides such as N-tert-butyl-N-fluorobenzenesulfonamide are useful in the fluorination of alkenyl iodides. N-Fluoro-N-alkylsulfonamides are disadvantageous to use because in preparation, N-fluoro-N-alkylsulfonamides are difficult to isolate and thus, require either column chromatography or low pressure distillation and organometallics or strongly basic anions cause .beta.-elimination of HF from the reagent.
U.S. Pat. No. 4,828,764; J. Foropoulos, Jr. et al., "Synthesis, Properties, and Reactions of Bis((trifluoromethyl)sulfonyl)imide, (CF.sub.3 SO.sub.2).sub.2 NH", Inorg. Chem, 23, 3720 (1984).; S. Singh et al., "N-Fluoroperfluoroalkylsulfonimides: Remarkable New Fluorination Reagents", J. Am. Chem. Soc. 109, 7194 (1987); G. Resnati et al., "N-Fluorobis[(trifluoromethyl)sulfonyl]imide: An Efficient Reagent for the .alpha.-Fluorination of Functionalized Carbonyl Compounds", J. Org. Chem. 56, 4925 (1991); and D. Desmarteau et al., "N-Fluoro-N-Bis(trifluoromethanesulfonyl)imide--An Improved Synthesis", J. Fluorine Chem. 52, 7 (1991) teach that N-fluoroperfluoroalkylsulfonimides such as N-fluoro-bis(trifluoromethanesulfonyl)imide are useful in the fluorination of organic compounds. Unfortunately, N-fluoroperfluoroalkylsulfonimides are disadvantageous to use because a five step synthesis for their preparation is required, they are very hydroscopic, they cannot be used with aromatic solvents such as benzene or toluene because they react with these solvents, and they require special handling because they react with glass.
F. Davis et al., "N-Fluoro-o-benzenedisulfonimide: A Useful New Fluorinating Reagent", Tetrahedron Letters 32(13), 1631 (1991) teach that N-fluoro-o-benzenesulfonimide is useful in the fluorination of enolates and carbanions.
N-Fluoro-p-fluoro-benzenesulfonimide is known from D. Barton et al., J. Chem. Soc. Perkin Trans. 1, 732 (1974) but the reference does not teach any use for N-fluoro-p-fluoro-benzenesulfonimide.
Thus, there was a need in the art for a new electrophilic fluorinating agent which is easy to make and fluorinates less reactive nucleophiles. To a great extent such need was met by the novel fluorinating agents disclosed in the commonly assigned U.S. application Ser. No. 843,692 filed Feb. 28, 1992. Surprisingly, it was found that these N-fluorosulfonimides (See Formula I infra) behave as electrophilic fluorinating agents which combine safe handling and easy access with the capacity to fluorinate nucleophiles ranging from aromatics to carbanions.
The previous art prepared N-fluorosulfonimides by basically two methods. One method involved the preparation of N-fluorosulfonimides by direct fluorination of the imide. The direct fluorination is depicted by the following equation. EQU R.sub.1 O.sub.2 S--NH--SO.sub.2 R.sub.2 +F.sub.2 .increment.R.sub.1 O.sub.2 S--N--FSO.sub.2 R.sub.2 +HF 1.
As can be seen, the fluorine replaces the imido hydrogen yielding the N-fluoroimide and hydrogen fluoride (HF) as a by-product. This method is significantly disadvantageous since HF is a very hazardous by-product. In another method, R. E. Banks et al. disclose preparing perfluoro-[N-fluoro-N-(4-pyridyl)methanesulphonamide] (III) by fluorination of the sodio derivative of perfluoro-[N-(4-pyridyl)methanesulphonamide] in pure acetonitrile solvent. Banks et al. also note that theoretically (CF.sub.3 SO.sub.2).sub.2 NH might be convertable to (CF.sub.3 SO.sub.2).sub.2 NF via the sodium salt (CF.sub.3 SO.sub.2).sub.2 NNa.
In spite of the novel fluorinating compounds and the above methods of preparation, advancement is still sought in this field for improved synthesis steps which reduce processing and handling requirements, environmental hazards and costs associated with commercial processing methods. Such advancement is provided by the present invention.